SAYSD1

Summary

SAYSD1 (SAYSVFN motif domain containing 1, HGNC:21025) is a protein-coding gene on chromosome 6p21.2, encoding SAYSvFN domain-containing protein 1 (Q9NPB0). Ufmylation ‘reader’ component of a translocation-associated quality control pathway, a mechanism that takes place when a ribosome has stalled during translation, and which is required to degrade clogged substrates.

Enables UFM1-modified protein reader activity. Involved in protein quality control for misfolded or incompletely synthesized proteins and rescue of stalled ribosome. Located in intracellular membrane-bounded organelle. Is active in endoplasmic reticulum.

Source: NCBI Gene 55776 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_018322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21025
Approved symbol	SAYSD1
Name	SAYSVFN motif domain containing 1
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11101
Ensembl gene	ENSG00000112167
Ensembl biotype	protein_coding
Entrez	55776

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 nonsense_mediated_decay, 1 protein_coding

ENST00000229903, ENST00000373249, ENST00000481599, ENST00000703663, ENST00000703664

RefSeq mRNA: 2 — MANE Select: NM_018322 NM_001304793, NM_018322

CCDS: CCDS4840

Canonical transcript exons

ENST00000229903 — 2 exons

Exon	Start	End
ENSE00001459875	39114883	39115186
ENSE00003848392	39104063	39105776

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2118 / max 145.7004, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73471	7.2027	1734
73470	4.0091	1498

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.12	gold quality
right testis	UBERON:0004534	95.04	gold quality
sperm	CL:0000019	94.79	gold quality
testis	UBERON:0000473	93.35	gold quality
male germ cell	CL:0000015	91.50	gold quality
adult organism	UBERON:0007023	89.52	gold quality
calcaneal tendon	UBERON:0003701	88.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.93	gold quality
islet of Langerhans	UBERON:0000006	87.43	gold quality
oocyte	CL:0000023	87.25	gold quality
secondary oocyte	CL:0000655	86.97	gold quality
cortical plate	UBERON:0005343	85.46	gold quality
mucosa of transverse colon	UBERON:0004991	84.82	gold quality
ganglionic eminence	UBERON:0004023	84.14	gold quality
pancreas	UBERON:0001264	82.99	gold quality
ventricular zone	UBERON:0003053	82.71	gold quality
body of pancreas	UBERON:0001150	82.67	gold quality
granulocyte	CL:0000094	81.86	gold quality
tibia	UBERON:0000979	81.76	gold quality
rectum	UBERON:0001052	81.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.65	gold quality
gall bladder	UBERON:0002110	81.56	gold quality
right adrenal gland cortex	UBERON:0035827	81.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.27	gold quality
metanephros cortex	UBERON:0010533	81.17	gold quality
endocervix	UBERON:0000458	81.09	gold quality
minor salivary gland	UBERON:0001830	80.90	gold quality
right adrenal gland	UBERON:0001233	80.87	gold quality
transverse colon	UBERON:0001157	80.84	gold quality
stromal cell of endometrium	CL:0002255	80.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

64 targeting SAYSD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4311	99.31	70.47	3041

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	saysd1	ENSDARG00000043687
mus_musculus	Saysd1	ENSMUSG00000045107
rattus_norvegicus	Saysd1	ENSRNOG00000088418
drosophila_melanogaster	Saysd1	FBGN0039291
caenorhabditis_elegans		WBGENE00015744

Protein

Protein identifiers

SAYSvFN domain-containing protein 1 — Q9NPB0 (reviewed: Q9NPB0)

All UniProt accessions (5): A0A994J3Z7, A0A994J4E3, A0A994J6I1, A0A9H3ZQQ3, Q9NPB0

UniProt curated annotations — full annotation on UniProt →

Function. Ufmylation ‘reader’ component of a translocation-associated quality control pathway, a mechanism that takes place when a ribosome has stalled during translation, and which is required to degrade clogged substrates. Specifically recognizes and binds ufmylated ribosomes when a ribosome has stalled, promoting the transport of stalled nascent chain via the TRAPP complex to lysosomes for degradation.

Subunit / interactions. Associates (via N-terminus) with ribosomes.

Subcellular location. Endoplasmic reticulum membrane. Cytoplasmic vesicle membrane.

Domain organisation. The middle helical (MH) region recognizes and binds ufmylated ribosomes.

Similarity. Belongs to the SAYSD1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPB0-1	1	yes
Q9NPB0-2	2

RefSeq proteins (2): NP_001291722, NP_060792* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019387	SAYSvFN_dom	Domain
IPR039159	SAYSD1	Family

Pfam: PF10260

UniProt features (12 total): mutagenesis site 3, topological domain 2, region of interest 2, splice variant 2, chain 1, intramembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPB0-F1	66.34	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (3):

Position	Phenotype
7–14	abolished interaction with ribosomes.
150–156	in 7a mutant; abolished involvement in the translocation-associated quality control pathway.
5–12	in 3a mutant; abolished interaction with ribosomes.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATION, MODULE_205, BRN2_01, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, GOBP_TRANSLATIONAL_ELONGATION, LEE_AGING_CEREBELLUM_DN, MODULE_95, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_ORGANELLE_DISASSEMBLY, TGGAAA_NFAT_Q4_01, NUYTTEN_EZH2_TARGETS_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (2): protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), rescue of stalled cytosolic ribosome (GO:0072344)

GO Molecular Function (1): UFM1-modified protein reader activity (GO:0141185)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytoplasmic vesicle membrane (GO:0030659), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
protein catabolic process	1
cytoplasmic translational elongation	1
ribosome disassembly	1
ubiquitin-like protein reader activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vesicle membrane	1
cytoplasmic vesicle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAYSD1	DHRS7C	A6NNS2	649
SAYSD1	DNAH8	Q96JB1	648
SAYSD1	MCRIP1	C9JLW8	617
SAYSD1	TPGS2	Q68CL5	584
SAYSD1	C5orf22	Q49AR2	580
SAYSD1	TRMT13	Q9NUP7	566
SAYSD1	PIGH	Q14442	463
SAYSD1	CHAMP1	Q96JM3	460
SAYSD1	KCNK17	Q96T54	447
SAYSD1	NXT2	Q9NPJ8	443
SAYSD1	RCVRN	P35243	438
SAYSD1	DCAF10	Q5QP82	431
SAYSD1	KCNK16	Q96T55	418
SAYSD1	LYRM1	O43325	400
SAYSD1	CYP27C1	Q4G0S4	400

IntAct

14 interactions, top by confidence:

A	B	Type	Score
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
SAYSD1	UBE2DNL	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
SAYSD1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SAYSD1	NDUFB3	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC35F2	EI24	psi-mi:“MI:0914”(association)	0.350
SMC5	DKFZp686H10254	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (42): SAYSD1 (Affinity Capture-MS), SAYSD1 (Affinity Capture-MS), SAYSD1 (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), SAYSD1 (Affinity Capture-MS), REEP5 (Affinity Capture-MS), BCS1L (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), REEP6 (Affinity Capture-MS), ABCC4 (Affinity Capture-MS), SAYSD1 (Affinity Capture-MS), FAM134C (Affinity Capture-MS), NDUFA7 (Affinity Capture-MS), AP5Z1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: Q32L85, Q8K190, Q9NPB0, Q9VBW0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

23 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

737 predictions. Top by Δscore:

Variant	Effect	Δscore
6:39115073:G:C	donor_gain	1.0000
6:39105773:CTTC:C	acceptor_gain	0.9900
6:39105775:TCCTA:T	acceptor_loss	0.9900
6:39105785:C:CT	acceptor_gain	0.9900
6:39105787:C:CT	acceptor_gain	0.9900
6:39105788:A:T	acceptor_gain	0.9900
6:39114554:A:C	donor_gain	0.9900
6:39105774:TTC:T	acceptor_gain	0.9800
6:39105777:C:CC	acceptor_gain	0.9800
6:39105782:A:C	acceptor_gain	0.9800
6:39105791:C:CT	acceptor_gain	0.9800
6:39113562:T:TA	donor_gain	0.9800
6:39113569:AT:A	donor_gain	0.9800
6:39114526:T:A	donor_gain	0.9800
6:39115078:CCG:C	donor_gain	0.9800
6:39105775:TC:T	acceptor_gain	0.9700
6:39105776:CC:C	acceptor_gain	0.9700
6:39105795:C:CT	acceptor_gain	0.9700
6:39106757:TGTC:T	donor_gain	0.9700
6:39114488:TGC:T	donor_gain	0.9700
6:39105782:A:AC	acceptor_gain	0.9600
6:39105792:A:T	acceptor_gain	0.9600
6:39106797:AAGAC:A	donor_gain	0.9600
6:39114516:CCTT:C	donor_gain	0.9600
6:39113538:A:C	donor_gain	0.9500
6:39114877:TCTCA:T	donor_loss	0.9500
6:39114878:CTCA:C	donor_loss	0.9500
6:39114879:TCA:T	donor_loss	0.9500
6:39114880:CA:C	donor_loss	0.9500
6:39114881:A:AT	donor_loss	0.9500

AlphaMissense

1147 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:39105519:G:C	F155L	0.996
6:39105519:G:T	F155L	0.996
6:39105521:A:G	F155L	0.996
6:39105659:A:G	W109R	0.994
6:39105659:A:T	W109R	0.994
6:39105534:G:C	S150R	0.988
6:39105534:G:T	S150R	0.988
6:39105536:T:G	S150R	0.988
6:39105520:A:C	F155C	0.987
6:39105520:A:G	F155S	0.986
6:39105521:A:T	F155I	0.985
6:39105530:A:G	Y152H	0.983
6:39105611:A:C	Y125D	0.983
6:39105521:A:C	F155V	0.982
6:39105604:A:T	V127D	0.977
6:39105516:A:C	N156K	0.976
6:39105516:A:T	N156K	0.976
6:39105499:A:G	I162T	0.975
6:39105499:A:T	I162N	0.974
6:39115066:A:C	F8L	0.974
6:39115066:A:T	F8L	0.974
6:39115068:A:G	F8L	0.974
6:39105494:C:G	G164R	0.971
6:39105523:A:T	V154E	0.971
6:39105532:G:T	A151D	0.970
6:39105590:A:C	Y132D	0.969
6:39105527:A:G	S153P	0.968
6:39105587:A:G	W133R	0.968
6:39105587:A:T	W133R	0.968
6:39105619:C:T	G122D	0.967

dbSNP variants (sampled 300 via entrez): RS1000276069 (6:39107890 C>A,T), RS1000653880 (6:39112459 G>A), RS1001129153 (6:39106234 T>C), RS1001176104 (6:39113433 GA>G), RS1001316555 (6:39106913 T>C), RS1002149605 (6:39111379 A>C,G), RS10023 (6:39104258 A>G,T), RS1002502048 (6:39111887 T>C), RS1002876453 (6:39116982 G>C), RS1003561221 (6:39110154 A>G), RS1003623619 (6:39110579 C>T), RS1003659847 (6:39115308 G>A), RS1003681365 (6:39108867 C>T), RS1004165801 (6:39115604 A>G), RS1004222244 (6:39109091 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001960_4	Eating disorders	2.000000e-06
GCST003205_2	Cardiovascular disease in hypertension (calcium channel blocker interaction)	3.000000e-06
GCST006119_2	Protein C levels	5.000000e-09
GCST007094_98	Diastolic blood pressure	9.000000e-10
GCST010479_1	Coronary artery disease	4.000000e-10
GCST012190_7	Body mass index and diastolic blood pressure (bivariate analysis)	7.000000e-06
GCST012191_7	Body mass index and systolic blood pressure (bivariate analysis)	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007767	response to calcium channel blocker
EFO:0004633	protein C measurement
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.